Living things differ from nonliving things in that they carry information stored in DNA and RNA. Much of what living cells need to do require them to integrate this stored information with information inputs from their external environments. In this way, cells are like computers, but, unlike computers, information handling by cells depends on molecules instead of electrons moving through wires. Over the past five years, we have developed and used advanced methods to study a very simple example of biological information handling, a system that a single yeast cell uses to sense and transmit information from outside to make decisions. We have learned about the molecules the cell uses to do this and some of the key operations these molecules perform. During the next five years, we will study carefully the molecular operations needed for one key portion of the information transmission system to function. We will learn how these molecular events affect the signal transmitted by the system and the information that the signal carries. In the shorter term, because closely related systems operate in all animal cells, including humans, what we learn about how the molecules operate may suggest avenues to devise drugs that manipulate their function and might afford useful therapies. Longer term, a better understanding of how molecular events perform operations on information may help guide genetic interventions, and might help contribute to development of molecular computation. PUBLIC HEALTH RELEVANCE: We will study the operation of one small part of a model information sensing and transmitting system in a model cell. We will learn how specific molecular operations regulate the signal and the information the signal transmits.